JP2021090803A - Occlusion device - Google Patents

Abstract

To provide an improved occlusion device for aneurysm treatment.SOLUTION: An occlusion device for intrasaccular implantation and/or vascular occlusion includes: (a) a substantially solid marker 16 having a proximal end and a distal end; and (b) a low profile resilient mesh body 14 attached to the distal end of the marker, the body having a delivery shape and a deployed shape capable of conforming to aneurysm walls, and having a diameter greater than a diameter φy of an aneurysm 10 to be treated.SELECTED DRAWING: Figure 1B

Description

Related Applications This application is a US patent provisional application No. 61 / 986,369, filed April 30, 2014, and a US patent provisional application No. 61 / 083,672, filed November 24, 2014. Claim the priority of the calligraphy. These disclosures are incorporated herein by reference in their entirety. In addition, all documents and references cited herein and in the above reference applications are incorporated herein by reference.

The present invention generally relates to the fields of occlusion devices and / or occlusion device systems and / or implantable occlusion devices, and their use for the treatment and / or amelioration of aneurysms.

There is great demand for the development of improved occlusive devices and / or systems for the treatment and / or improvement of aneurysms. This view is currently supported by the abundance and breadth of current occlusion devices and / or systems in the field of aneurysm treatment. However, there is still an unaddressed demand for providing aneurysm treatment and / or aneurysm treatment, especially for neurovascular aneurysms, with an occlusive device containing a minimal amount of fully recoverable, indwellable material.

Aneurysms are known to form when the dilation of an artery is thinly stretched by blood pressure. The fragile portion of the artery forms a ridge or spherical area at risk of leakage and / or rupture. When a neurovascular aneurysm ruptures, it causes bleeding into the subarachnoid space, which is the gap surrounding the brain, and causes subarachnoid hemorrhage. Subarachnoid hemorrhage due to a ruptured neurovascular aneurysm can lead to hemorrhagic stroke, brain damage and death. Approximately 25 percent of all patients with neurovascular aneurysms suffer from subarachnoid hemorrhage. Neurovascular aneurysms affect 2-5 percent of the population and, more commonly, affect women rather than men. It is estimated that as many as 18 million people currently living in the United States will develop neurovascular aneurysms in their lifetime. Every year, the number of cases of subarachnoid hemorrhage in the United States exceeds 30,000. 10 to 15 percent of these patients die before arriving at the hospital, and more than 50 percent die within the first 30 days after rupture. About half of those who are saved suffer from some form of permanent neuropathy.

Smoking, hypertension, traumatic head trauma, alcohol abuse, use of hormonal infertility, family history of cerebral aneurysms, and other hereditary factors such as Ehrers-Danlos syndrome (EDS), polycystic kidney disease and Marfan syndrome Disease may contribute to neurovascular aneurysms.

Most unruptured aneurysms are asymptomatic. Some people with unruptured aneurysms have the following symptoms: peripheral vision impairment, thinking or processing impairment, difficulty speaking, sensory disturbance, sudden changes in attitude, loss of balance and coordination, loss of concentration, short-term Experience some or all of memory difficulties and fatigue. Symptoms of a ruptured neurovasculature aneurysm include nausea and vomiting, neck stiffness or neck pain, blurred vision or diplopia, pain above and behind the eye, dilated pupils, photosensitivity, and loss of sensation. Patients, sometimes described as "the worst headaches of their lives," are experiencing one of the symptoms of a ruptured neurovascular aneurysm.

Most aneurysms remain undetected until a rupture occurs. However, aneurysms may be found during routine health examinations or diagnostic procedures for other health problems. Diagnosis of a ruptured cerebral aneurysm is generally made by detecting signs of subarachnoid hemorrhage by CT scan (computed tomography). If a CT scan is negative but a ruptured aneurysm is still suspected, a lumbar puncture is performed to detect blood in the cerebrospinal fluid that surrounds the brain and spinal cord.

To determine the exact location, size and shape of the aneurysm, neuroradiologists use either cerebral angiography or tomographic angiography. The conventional method of cerebral angiography involves introducing a catheter into an artery (usually in the lower extremities) and advancing it within a blood vessel of the body to the artery involved in the aneurysm. A special pigment called a contrast medium is injected into the patient's artery and its distribution is shown by X-ray projection. This method may not detect some aneurysms due to overlapping structures or spasms.

Computer tomographic angiography (CTA) is an alternative to conventional methods and can be performed without the need for arterial catheterization. This test combines a regular CT scan with an intravenous injection of contrast dye. When the dye is injected intravenously, it travels to the cerebral arteries and a CT scan is used to form an image. These images show exactly how blood flows into the cerebral arteries. The new diagnostic modalities are expected to complement both traditional and traditional diagnostic studies with minimally invasive imaging and can provide more accurate three-dimensional anatomical information for the pathology of aneurysms. There is sex. Better imaging, in combination with the development of improved minimally invasive treatments, will allow physicians to detect and treat more and more asymptomatic aneurysms before problems occur.

Several methods have been attempted to treat aneurysms, with varying degrees of success. For example, craniotomy is a procedure in which an aneurysm is identified and treated extravascularly. This type of procedure has major drawbacks. For example, the surgeon has to cut various tissues to reach the aneurysm, causing the patient to suffer significant trauma to the area of the aneurysm. To treat a cerebral aneurysm extravascularly, for example, the surgeon must generally remove part of the patient's skull and also damage the brain tissue to reach the aneurysm. Because of this, surgery can cause patients to develop epilepsy.

Other techniques used to treat aneurysms are performed intravascularly. Such techniques generally involve attempting to form a mass within the sac of the aneurysm. Generally, a microcatheter is used to access the aneurysm. The distal tip of the microcatheter is placed within the aneurysm sac and the microcatheter is used to inject the embolic material into the aneurysm sac. The embolic material includes, for example, a detachable coil or an embolic agent such as a liquid polymer. Injection of these types of embolic material has drawbacks, most of which are associated with the transfer of embolic material from the aneurysm to the parent artery. This can cause permanent and irreversible occlusion of the parent artery.

For example, when an aneurysm that does not have a well-defined cervical region is occluded with a detachable coil, the detachable coil can deviate from the aneurysm sac to the parent artery. In addition, it may be difficult to accurately measure how full the aneurysm sac is when the detachable coil is placed. Therefore, there is a risk of overfilling the aneurysm, again with the detachable coil flowing into the parent artery.

Another drawback of the detachable coil includes consolidation of the coil over time. After filling the aneurysm, space remains between the coils. The continuous hemodynamic force of the circulation acts to consolidate the coil mass, creating a cavity in the neck of the aneurysm. Therefore, the aneurysm may reopen.

The movement of embolic agents is also a problem. For example, if the liquid polymer is injected into the aneurysm sac, the hemodynamics of the system can cause the liquid polymer to deviate from the aneurysm sac. This can also lead to irreversible occlusion of the parent vessel.

Techniques have been attempted to address the shortcomings associated with the deviation of the embolic material into the parent vessel. Such techniques are, but are not limited to, temporary blood flow arrest and parenteral vascular occlusion, and generally do not result in blood flow to the parent vessel until a clot is formed within the aneurysm sac. As such, it involves the temporary occlusion of the parent vessel on the proximal side of the aneurysm. In theory, this reduces the tendency of the embolic material to deviate from the aneurysm sac. However, it has been found that thrombus clots can be dissolved by the usual lysis of blood. Also, in some cases, it is highly undesirable to occlude the parent vessel, even temporarily, from the perspective of patient risk / benefit. For this reason, this technique may not be available as a treatment option. In addition, it is now known that occluding the parent vessel does not prevent all embolic materials from deviating into the parent vessel.

Another intravascular technique for treating an aneurysm involves inserting a detachable balloon into the aneurysm's sac using a microcatheter. The detachable balloon is then inflated with saline and / or contrast fluid. The balloon is then detached from the microcatheter and left in the aneurysm sac in an attempt to fill the aneurysm sac. However, due to the drawbacks of detachable balloons, this approach has largely been superseded by current techniques of coil placement or other types of occlusion devices. For example, detachable balloons generally do not fit the internal structure of the aneurysm sac when inflated. Instead, withdrawal balloons require the aneurysm sac to be adapted to the outer surface of the withdrawal balloon. This increases the risk that the detachable balloon will rupture the aneurysm pouch. In addition, the detachable balloon may rupture and deviate from the aneurysm.

Another intravascular procedure for treating an aneurysm includes an occlusive device with two expandable lobes and waists, or an expandable body, neck and base.

Yet another intravascular technique for treating an aneurysm is an intracapsular occlusion device with a body portion designed to fill and / or radially expand the space within the aneurysm's sac. Including.

Such occlusion devices include, for example, US Pat. No. 5,025,060, US Pat. No. 5,928,260, US Pat. No. 6,168,622, US Pat. No. 6, 221.086, US Pat. No. 6,334,048, US Pat. No. 6,419,686, US Pat. No. 6,506,204, US Pat. No. 6,605, Specification 102, US Pat. No. 6,589,256, US Pat. No. 6,780,196, US Pat. No. 7,044,134, US Pat. No. 7,093,527 Specification, US Pat. No. 7,128,736, US Pat. No. 7,152,605, US Pat. No. 7,229,461, US Pat. No. 7,410,482. , U.S. Pat. No. 7,597,704, U.S. Pat. No. 7,695,488, U.S. Pat. No. 8,034,061, U.S. Pat. No. 8,142,456, U.S.A. Patent No. 8,261,648, US Pat. No. 8,361,138, US Pat. No. 8,430,012, US Pat. No. 8,454,633 and US Pat. No. 8,523,897, US Patent Application Publication No. 2003/0195553, US Patent Application Publication No. 2004/098027, US Patent Application Publication No. 2006/0167944, US Patent Application Publication 2007/0288083, US Patent Application Publication No. 2010/0069948, US Patent Application Publication No. 2011/0046658, US Patent Application Publication No. 2012/0283768, US Patent Application Publication No. 2012 / 0330341 and US Patent Application Publication No. 2013/0035712, European Patent No. 1651117, and International Publication No. 13/109309, all of which are referred to herein. The embodiments of the occlusion device disclosed in the document are not disclosed.

Therefore, the present invention provides innovative improvements and some advantages in the field of vascular occlusion devices. This is because the occlusion devices disclosed herein specifically provide aneurysm treatment and / or aneurysm treatment for neurovascular aneurysms by the use of minimal amounts of fully recoverable, indwellable materials. .. Such an increased size of the occlusive device configuration allows additional material for fastening the aneurysm neck and / or an anchor mechanism within the parent vessel adjacent to the aneurysm and / or into the aneurysm sac of the device. Eliminates the need for spherical, radial expansion of the body.

All documents and references cited herein and in reference are incorporated herein by reference.

INDUSTRIAL APPLICABILITY To provide aneurysm treatment and / or improvement by using a thin, fully recoverable, indwellable thin elastic mesh material that is sized relative to the diameter of the aneurysm. Designed an occlusion device. For this reason, occlusion devices with less material than current standard devices minimize the need for anticoagulant therapy and / or flow deep into the vascular tree and cause clot embolization that can cause stroke. Reduce risk. Such implantable occlusion devices are also used for the treatment of vascular occlusion and / or peripheral vascular embolism.

Disclosed herein are (a) a substantially solid marker with proximal and distal ends, and (b) a thin elastic mesh body attached to the distal end of the marker. In an occlusion device for intracapsular implantation, wherein the body has a delivery shape and an indwelling shape that is compatible with the aneurysm wall, and the body has a diameter larger than the diameter of the aneurysm to be treated. is there.

In another embodiment, the elastic mesh body of the occlusion device is a single layer mesh.

In another embodiment, the elastic mesh body of the occlusion device is a bilayer or bilayer mesh. In a further embodiment, the mesh bilayer comprises a single layer of the mesh folded in the circumferential direction.

In another embodiment, the indwelling shape of the elastic mesh body of the occlusion device can be juxtaposed to the aneurysm dome.

In another embodiment, the proximal end of the marker of the occlusion device can seal the aneurysm neck. In a further embodiment, the marker is a radiation opaque marker, the marker is a detachment connection for indwelling the obstruction device, and the marker is a mounting connection for retrieving the obstruction device. Includes a rigid member and / or the marker is a solid ring.

Also disclosed herein is a kit that includes an obstruction device disclosed herein and a delivery means for indwelling the obstruction device.

Also disclosed herein are (a) a substantially solid marker with proximal and distal ends and (b) a thin elastic mesh attached to the distal end of the marker. In an implantable device for vascular occlusion, including the body, the body having a delivery shape and an indwelling shape compatible with the vessel wall, the body having a diameter larger than the diameter of the vessel to be treated. is there.

In another embodiment, the body of the occlusion device is a single layer of mesh.

In another embodiment, the body of the occlusion device is a bilayer or bilayer of mesh. In a further embodiment, the mesh bilayer comprises a single layer of the mesh folded in the circumferential direction.

Further disclosed herein are (a) a substantially solid marker with proximal and distal ends, and (b) an elastic mesh body attached to the distal end of the marker. Implantation for vascular occlusion, including an elastic mesh body, wherein the body has a delivery shape and an indwelling shape that is compatible with the vessel wall, and the body is a double layer of mesh containing a circumferential fold line. It is a type device. In another embodiment, the elastic mesh body of the occlusion device is a thin elastic mesh body.

Further disclosed herein are (a) a substantially solid marker with proximal and distal ends, and (b) an elastic mesh body attached to the distal end of the marker. The body has a delivery shape and an indwelling shape that is compatible with the wall of the aneurysm or aneurysm, the body has a diameter greater than the diameter of the aneurysm or blood vessel to be treated, and the body. An occlusion device having a height of about 10-20% of its width.

Further disclosed herein are methods for manufacturing and / or delivering and / or indwelling the occlusion device disclosed herein.

In other embodiments, the obstruction device in the previous paragraph may incorporate either of the earlier or later embodiments disclosed.

The outline of the invention does not define the scope of claims or limit the scope of the present invention in any way.

Other features and advantages of the present invention will become apparent from the following drawings, detailed description and claims.

1A-1B show perspective views of an embodiment of the occlusion device disclosed herein. FIG. 1A shows the diameter (x) of the occlusion device in free gas. FIG. 1B shows a cross-sectional view of an occlusion device placed in an aneurysm having a diameter (y). 2A-2C show perspective views of an embodiment of delivery and / or indwelling of the occlusion device disclosed herein. FIG. 2A shows a device in its delivery shape. FIG. 2B shows a device in which the compressed ends of the mesh material are placed so that they open outward. FIG. 2C shows the device in its indwelling shape. 3A-3B show perspective views of an embodiment of the occlusion device disclosed herein. FIG. 3A shows the diameter (x) of the occlusion device having a bilayer or bilayer of circumferential fold lines and mesh material. FIG. 3B shows a bilayer occlusion device placed in an aneurysm having a diameter (y) disclosed herein. 4A-4C show perspective views of an embodiment of delivery and / or indwelling of the occlusion device disclosed herein. FIG. 4A shows a bilayer closure device in its delivery shape. FIG. 4B shows a bilayer closure device in which the compressed end of the device is placed so that it opens outward. FIG. 4C shows the flattening effect / increased width / increased diameter of the bilayer / bilayer of the mesh material of the device in its indwelling state. 5A-5B show perspective views of an embodiment of electrolytic delivery and / or indwelling and / or detachment of the occlusion device disclosed herein. FIG. 5A shows delivery of a double layer occlusion device by a catheter and / or guide wire with electrolytic means. FIG. 5B shows the electrolytic detachment of the core wire or guide wire from the obstruction device.

The present invention is shown in drawings and specifications in which similar elements are assigned the same reference numbers. However, although specific embodiments are shown in the drawings, there is no intention to limit the invention to the specific embodiments (s) or embodiments (s) disclosed. Rather, the invention is intended to include all modifications, alternative structures and equivalents within the scope and intent of the invention. Therefore, the drawings are exemplary and are not intended to be limiting.

Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the technology belongs.

Illustrative embodiments of the present invention are shown in FIGS. 1 to 5.

For the purposes of the present invention, the term "corresponds to" means that there is a functional and / or mechanical relationship between objects that correspond to each other. For example, a blockage device delivery system corresponds to (or is compatible with) a blockage device for its detention.

For the purposes of the present invention, the term "occlusion device" is such as "device" or "occlusion device system" or "occlusion system" or "system" or "occlusion device implant" or "implant" or "intracapsular implant". May be interchangeable with and / or meaning terms not limited to these.

Blocking device delivery systems are well known in the art and readily available. For example, such sending techniques include US Patent No. 4,991,602, US Patent No. 5,067,489, US Patent No. 6,833,003, US Patent Application Publication No. It can be described in, but is not limited to, 2006/0167494 and US Patent Application Publication No. 2007/0288083. Each of these teachings is incorporated herein by reference. For the purposes of the present invention, any kind of obstruction device sending means and / or sending system and / or sending technology and / or sending mechanism and / or detachment (and / or mounting) means and / or detachment system and / or detachment technique. And / or the withdrawal mechanism may be used (as correspondingly) and / or modified in a manner that is compatible with the occlusion device disclosed herein. Exemplary occlusion device delivery mechanisms and / or systems include, but are not limited to, guide wires, pusher wires, catheters, microcatheter, and the like. Examples of the closing device release mechanism include, but are not limited to, a fluid pressure, an electrolytic mechanism, a hydraulic mechanism, an interlock mechanism, and the like. In one embodiment, the occlusion device disclosed herein is used in a method of electrolytic withdrawal. Electrolytic withdrawal is well known in the art, for example, US Pat. No. 5,122,136, US Pat. No. 5,423,829, US Pat. No. 5,624,449, US Pat. Can be described in Japanese Patent No. 5,891,128, US Pat. No. 6,123,714, US Pat. No. 6,589,230 and US Pat. No. 6,620,152. ..

1A and 3A show an embodiment of an occlusive device for intracapsular implantation in an aneurysm 10 to be treated, disclosed herein. 1A and 3A also show "free gas".
The diameter (x) of the elastic mesh body 14 of such an occlusion device inside is shown. As accepted in the art, the diameter of such occlusion devices is measured in free gas. Therefore, in an object and one embodiment of the present invention, the elastic mesh body 14 of the occlusion device is "enlarged" with respect to the aneurysm 10 and is therefore shown in FIGS. 1A and 1B and FIGS. As shown, it has a diameter (x) greater than the diameter (y) of the aneurysm 10 to be treated (ie, Φx> Φy). That is, as long as the mesh body 14 is sized to sufficiently seal the neck 22 of the aneurysm 10 and cause clot formation and / or healing of the aneurysm 10, the diameter (y) is. It is the maximum diameter of the aneurysm 10 to be treated, or one of the larger diameters of the aneurysm 10. An exemplary range of occlusion device diameter (x) disclosed herein is about 6-30 millimeters (mm), and an exemplary diameter (y) of an aneurysm to be treated is x. Is less than the value of. For example, the diameter (x) of the occlusion device is either 7 mm, 11 mm and / or 14 mm. In one embodiment, the positions of the distal ends 34 of the substantially solid marker 16 are attached approximately equidistant from both ends of the elastic mesh body 14. Such an arrangement of the markers 16 on the intracapsular elastic mesh body 14 provides full recoverability of the occlusion device disclosed herein.

In another embodiment, the occlusion device disclosed herein is "sized up" for any vessel to be treated in a pathological condition in which vascular occlusion is desired, such as peripheral vascular disease. Ru ". In this example, the diameter (x) of the occlusive device is greater than the diameter (z) of any vessel to be treated, as long as the body 14 of the occlusive device fits into the vessel wall and promotes blood clot formation. large.

1B and 3B show an embodiment of an occlusion device indwelling within an aneurysm 10 to be treated, disclosed herein. 1B and 3B show the diameter (y) of such an aneurysm 10 to be treated, and blood flow in the parent vessel 12 (and basilar artery) adjacent to the aneurysm 10 and its neck 22. (Arrow) is also shown. In one embodiment, the elastic mesh body 14 of the occlusion device has a "thin" configuration when in free gas and when indwelled.

For the purposes of the present invention, the term "low profile" means that the elastic mesh body 14 has a height 32 in free gas, which is about 10-20% of its width, and thus its indwelling shape. In, the elastic mesh body 14 is placed flush with each other in a flat state, rises against the wall of the aneurysm 10, covers at least the inner surface of the lower 20 of the aneurysm 10, and seals the neck 22 of the aneurysm 10. It means that it is arranged to stop. Thus, the occlusion device disclosed herein expands to occlude the dome space of the aneurysm 10 (completely and / or partially with respect to most of the space within the aneurysm 10). Lower and / or thinner than occlusion devices readily available in the art, extending radially and / or expanding into a spherical state. In one embodiment, the elastic mesh body 14 has a height 32 in free gas, which is about 12-18% of its width. In another embodiment, the elastic mesh body 14 has a height 32 in free gas, which is about 14-16% of its width. In another embodiment, the elastic mesh body 14 has a height 32 of about 15% of its width in free gas. In one embodiment, the indwelling shape of the thin elastic mesh body 14 covers about 40% to 80% of the internal surface area of the dome of the aneurysm 10. In another embodiment, the indwelling shape of the thin elastic mesh body 14 covers about 50% to 70% of the internal surface area of the dome of the aneurysm 10. In another embodiment, the indwelling shape of the thin elastic mesh body 14 covers about 60% of the internal surface area of the dome of the aneurysm 10.

In another embodiment, the thin wing shape and / or open, expanded configuration of the body 14 is a single layer elastic mesh material. In another embodiment, the thin, extended and spread configuration is an elastic mesh material with double (or two) layers 24. As mentioned above, such an elastic mesh body 14 is "larger in size" than the aneurysm 10 to be treated, and thus the mesh body 14 is the diameter of the aneurysm 10 to be treated ( y) (ie, as long as the mesh body 14 is sized to sufficiently seal the neck 22 of the aneurysm 10 and cause clot formation and / or healing of the aneurysm 10) It has a diameter (x) greater than the maximum diameter of the aneurysm 10 to be made, or one of the larger diameters). The thin and large size of the elastic mesh body 14 has the ability to fit the inner surface of the wall of the aneurysm 10 (due to the opposing pressure of the body 14 against the wall of the aneurysm 10). Granted, thus, the occlusion device, at least only the lower 20 of the aneurysm 10 (ie, in a low volume flat state) dilates along the wall of the aneurysm 10, thereby the neck of the aneurysm 10. Eliminates the need for material to retain 22 and / or to secure within the parent vessel 12 (and thereby minimizes the need for anticoagulant therapy). Thus, the wing-like spread and / or dilated spread of the body 14 fits into the internal surface of the aneurysm 10 and is juxtaposed in the dome of the aneurysm 10. Such a configuration promotes the sealing of the neck 22 of the aneurysm 10, and thus promotes clot formation and / or healing and / or shrinkage of the aneurysm 10, and the size or size of the aneurysm 10 causes pain in the patient. Or it is especially advantageous if it is the cause of other side effects. Such a configuration also eliminates the need to block or substantially close the space in the dome of the aneurysm 10 in a spherically radial direction, as it requires only the minimum amount of elastic mesh material. It is advantageous. In particular, such an occlusion device is suitable for adaptation to a wide range of aneurysm 10 morphologies, as it is well known and generally accepted that the aneurysm 10 is not perfectly spherical in shape. Also, the occlusion device disclosed herein, which has "minimal" material, or less material than current standard devices, minimizes the need for anticoagulant therapy and / or It is advantageous because it reduces the risk of clot embolization, which can flow deep into the vascular tree and cause stroke.

In another embodiment of the occlusion device disclosed herein, the single layer or double layer 24 of the elastic mesh material of the thin device is such as a configuration in which 72 Nitinol (NiTi) wire mesh strands are woven. Includes, but is not limited to, a relatively uniform distribution of wire mesh strands or braids. In other embodiments, the occlusion device comprises a wire mesh strand or braid in a configuration in which NiTi strands in the range 36-144 are braided.

In another embodiment, as shown in FIGS. 3A-3B and 4A-4C, the bilayer 24 occlusion device disclosed herein is folded circumferentially (circumferential folding line 26). ), And for this reason, it is a wire mesh configuration that is itself folded back. The end of the double or folded layer 24 intersects a marker 16 located approximately centrally in the body 14 of the device. In this regard, the device is assembled by folding the mesh single layer material itself circumferentially along the preferred fold line 26 to effectively obtain an occlusion device containing the wire mesh material bilayer 24. That is, the mesh bilayer 24 includes a single layer of mesh folded in the circumferential direction (polygonal chain 26 in the circumferential direction). Although not bound by theory, the bilayer or bilayer 24 of this wire mesh material has a mechanism of action that is believed in animal studies to contribute to the enhancement of acute thrombus formation in the device. Trigger. Localization of a small amount of blood clots between the bilayer / bilayer 24, which has a large surface area contribution from the wire strands, is believed to promote thrombus nucleation and stabilization. In the indwelling shape, the body 14 with the folded double layer 24 is located deeper compared to the non-indwelled double layer 24 occlusion device, which corresponds to a width change of about 15% and markers. It is replaced by an increase in the diameter (x) of the device when pressure is applied to 16. This change in width / increase in diameter (x) is an effective anchoring function of the indwelling device as blood applies pressure to the mesh body 14 distributed across the neck 22 of the aneurysm 10. Is. Such a configuration also provides sufficient juxtaposition of the body 14 of the device with respect to the wall or vessel wall of the aneurysm 10 for peripheral arterial or venous occlusion. Based on animal studies to date, it is clear that the devices disclosed herein provide sufficient mesh density to provide acute hemostatic rest. Furthermore, based on analysis of the device after indwelling, it is known that the wire mesh / braid distribution remains relatively uniform.

1B and 4B also show the location of the marker 16 with the proximal and distal ends 34 on the occlusion device of the present invention. The distal end 34 of the marker 16 is attached to the elastic mesh body 14 of the occlusion device. A proximal end 36 of a marker 16 resting across the 22 neck of the aneurysm 10 to be treated in a bridge-like manner is shown. The proximal end 36 of the marker 16, combined with the properties of the thin elastic mesh body 14, eliminates the need to incorporate additional material to anchor the neck 22 of the aneurysm 10 and / or as an anchor within the parent vessel 12. , Offering the advantage of full recoverability of the device.

In one embodiment, the occlusion device marker 16 disclosed herein is a solid ring or the like made of a material such as, but not limited to, gold, platinum, stainless steel and / or a combination thereof. However, it is a substantially solid collar or rigid member, but not limited to these. In another embodiment, radiation impermeable materials such as, but not limited to, gold, platinum, platinum / iridium alloys and / or combinations thereof can be used. Such markers 16 provide visualization of the device during delivery and placement. The marker 16 is arranged within the occlusion device so that the proximal end 36 of the marker 16 can rest above the neck 22 of the aneurysm 10. The solidity of the marker 16 assists in imparting stability of the device within the aneurysm 10 and prevents movement or transmission of force through the elastic mesh of the body 14, thereby mispositioning or accidental movement of the device. To prevent. The marker 16 is also configured to provide a connection for ejecting / attaching from a corresponding delivery means, such as, but not limited to, a delivery catheter or guide wire and / or pusher wire 18 technology in conjunction with each other. ing. This also advantageously provides full recoverability of the devices disclosed herein.

In another embodiment, the substantially solid marker 16 is a radiation impermeable material such as, but not limited to, platinum, gold, platinum / iridium alloys and / or combinations thereof. Includes, facilitates visualization of occlusion devices under fluoroscopy during delivery, placement and / or placement. The marker 16 includes a proximal end 36 and a distal end 34. The elastic mesh body 14 may be attached to the distal end 34 and the proximal end 36 of the marker 16 may be configured to influence the shape, diameter and / or curvature of the elastic mesh body 14 when the occlusion device is expanded. .. The marker 16 may be designed in various shapes to influence the overall outer shape of the occlusion device to ensure an appropriate fit of the dilated / indwelling occlusion device within the aneurysm 10 capsule.

2A-2C and 4A-4C are exemplary means for delivering and / or indwelling the occlusion device disclosed herein through a blood vessel adjacent to an artery 12 and / or an aneurysm 10. Is shown. In one embodiment, as shown in FIGS. 2A and 4A, the occlusion device is closed and compressed through a pusher wire 18 mechanism such that the thin body 14 is closed or compressed in itself. (Sending shape) is sent. When the device is pushed into and / or placed in the aneurysm 10 sac, the end of the thin elastic mesh body 14 opens outward (as shown in FIGS. 2B and 4B) to open the body. 14 then fits into the wall of the aneurysm 10, with the marker 16 resting across the neck 22 and the thin body 14 being placed flush with the flat (indwelling shape) of at least the aneurysm 10. It covers the lower part 20 and makes it possible to seal the neck 22 of the aneurysm 10. In one embodiment, as shown in FIGS. 2C and 4C, the device is a single layer (FIG. 2C) that corresponds to a change in the width of the device and an increase in diameter (x) when pressure is applied to the marker 16. ) Or the double layer 24 (FIG. 4C) device shows deepening and / or flattening. This change in width / increase in diameter (x) is due to the effective anchoring function of the indwelling device as blood applies pressure to the body 14 distributed across the neck 22 of the aneurysm 10. is there. The results of animal studies described herein show that the circumferentially folded / double layer 24 configuration is the mesh body 14 of the device against the aneurysm 10 wall or blood vessel due to peripheral arterial or venous occlusion. We support providing efficient juxtaposition.

5A-5B provide exemplary means for electrolytically delivering and / or placing and / or detaching the occlusion device disclosed herein through a blood vessel adjacent to an artery 12 and / or an aneurysm 10. Shown. Electrolytic withdrawal means and methods, such as US Pat. No. 5,122,136, are well known in the art. In one embodiment, the coiled core wire 28 (or guide wire) of the catheter (or microcatheter) is the bilayer 24 disclosed herein within the marker 16 and at its distal end 34. Attached to the occlusion device (as shown in FIG. 5A). The coil winding maintains a constant diameter (Φ) so as not to affect the flexibility or rigidity of the delivery catheter or microcatheter or guidewire. In certain embodiments, a FEP (fluorinated ethylene propylene) heat shrink tube accommodates a coiled portion 28 of the core wire. Many readily available and well-known attachment techniques in the medical device technology field can be used to attach the distal end of the core wire to the inside of the marker band 16 and to the occlusion device or implant. Such mounting techniques include, but are not limited to, adhesives, laser melting, laser tack, spots and / or continuous welding. In one embodiment, an adhesive is used to attach the distal end of the core wire to the inside of the marker band 16. In a further embodiment, the adhesive is an epoxy material that is cured or cured by the application of heat or UV (ultraviolet) radiation. In a further embodiment, the epoxies are described in 14 Fortune Drive, Billerica, Mass. Located in Epoxy Technology, Inc. , A heat-cured two-part epoxy, such as EPO-TEK® 353ND-4, available from. Such an adhesive or epoxy material encapsulates the core wire connection inside the marker band, increasing its mechanical stability.

In another embodiment, during and / or after indwelling the device, the coiled core wire 28 places the double layer 24 obstruction device disclosed herein in an electrolytic detachment position (or) of the core wire itself. At region 30), the core wire is cut and / or dissolved by electrolysis at the base of the marker band 16 (as shown in FIG. 5B). This action then releases and / or places the bilayer 24 occlusion device within the aneurysm or vessel to be treated.

In certain embodiments, the thin elastic mesh body 14 of the occlusion device disclosed herein can be filled with an embolic material to promote coagulation and closure of the aneurysm 10.

In other embodiments, the enlarged occlusion device disclosed herein includes coiling techniques, framing coils, embolic agents, additional markers, polymers, absorbent polymers and / or combinations thereof. Auxiliary elements and / or members may be further incorporated.

Elastic mesh materials for designing and / or manufacturing occlusion devices are readily available and well known to those of skill in the art. Thus, elastic mesh materials include, but are not limited to, a variety of available materials such as, but not limited to, nickel titanium (Nitinol or otherwise known as NiTi), stainless steel, polymers and / or combinations thereof. Included in the range. Examples of well-known medical polymers include polyphosphazenes, polyacid anhydrides, polyacetals, polys (orthoesters), polyphosphoesters, polycaprolactones, polyurethanes, polylactides, polycarbonates, and polyamides. Classes and / or polymers such as combinations thereof, but are not limited thereto. (See, for example, J Polym Sci B Polymer Phys. Author manuscript; available at PMC 2012 June 15.)

In one exemplary embodiment, the elastic mesh material is formed of woven strands of a polymeric material such as, but not limited to, nylon, polypropylene or polyester. The polymer strands can be filled with a radiopaque material, which allows the physician treating the aneurysm to visualize the location of the device in the vascular system under fluoroscopy. The radiation-impermeable filler material preferably contains a radiation-impermeable dye such as bismuth trioxide, tungsten, titanium dioxide or barium sulfate, or iodine. The elastic mesh material can be formed by strands of radiation impermeable material. Radiation opaque strands allow physicians and / or radiologists to visualize the location of the mesh under fluoroscopy without the use of packed polymer materials. Such radiation opaque strands may be formed of materials such as, but not limited to, gold, platinum, platinum / iridium alloys and / or combinations thereof. In one embodiment, the elastic mesh material is composed of 10% to 20% platinum core NiTi. In another embodiment, the elastic mesh material is composed of 10% platinum core NiTi, 15% platinum core NiTi or 20% platinum core NiTi. A 10% platinum core NiTi structure is sufficient to provide a ghost image of the occlusion device under x-ray.

Combination wires or composite wires of this configuration with a radiation opaque core and a non-radiation opaque outer layer or casing are readily available and in the medical device and metal technology fields, DFT ( Registered Trademark) (Stretched Filled Tube) Well known as wire, cable or ribbon. A DFT® wire is a metal-metal composite material made to combine the desired physical and mechanical properties of two or more materials into a single wire. By placing a more radiopaque, but more ductile material within the core of the wire, the NiTi outer layer can impart mechanical properties similar to 100% NiTi wire to the resulting composite wire. it can. DFT® wire is available from Fort Wayne, Ind. , U.S. S. Fort Wayne Metals Corp. located in A. It is available from. See also, for example, an article in the journal entitled Biocompatible Will by Schaffer in Advanced Materials & Processes, Oct 2002, pages 51-54, which is incorporated herein by reference.

If the elastic mesh material is formed of radiation-impermeable metal strands, the strands may be coated with a polymer coating or extruded product. The coating or extruded product on the radiation opaque wire strands may not only provide visualization under fluoroscopy, but may also increase the resistance of the strands to bending fatigue as well as the lubricity of the strands. In one embodiment, the polymer coating or extruded product is coated or treated with a drug that tends to prevent coagulation, such as heparin. Coatings that prevent such blood clots are generally known. The polymer coating or extruded product can be any suitable extrudable polymer or any polymer that can be applied with a thin coating, such as Teflon® or polyurethane.

In yet another embodiment, the strands of elastic mesh material are formed using strands woven with both metal and polymer. Combining metal strands and polymer strands into a braid changes the flexibility properties of the mesh. The force required to place and / or fold such a mesh portion is significantly reduced compared to the force required for the mesh portion containing only the metal mesh strands. However, the radiation impermeable properties of the mesh for fluoroscopic visualization are maintained. Metal strands forming such devices include, but are not limited to, stainless steel, gold, platinum, platinum / iridium, nitinol and / or combinations thereof. Polymer strands forming this device may include nylon, polypropylene, polyester, Teflon® and / or combinations thereof. Further, the polymer strands of the mesh material are, but are not limited to, by using gold deposition on the polymer strands, or by using ion beam plasma deposition of suitable metal ions on the polymer strands. Well-known techniques can be used to chemically modify them to make them radiation opaque.

Elastic mesh materials can also be formed by filaments or strands with different diameters and / or different flexibility. By changing the size or flexibility of the polymer strands, the flexibility properties of the mesh during indwelling can also be changed. By varying the flexibility properties, both the indwelling and folded configurations of the elastic mesh body 14 can be transformed or altered into virtually any desired shape.

Not only can the mesh be formed of both polymer strands or filaments and metal strands or filaments, but the mesh can also be formed using filaments of different polymeric materials. For example, different polymeric materials with different flexibility properties can be used to form the mesh. This changes the flexibility properties and the resulting configuration of the mesh body 14 in both the indwelling and folded states. Such medical polymers are known and available in the art and are polyphosphazenes, polyacid anhydrides, polyacetals, polys (orthoesters), polyphosphoesters, polycaprolactones, polyurethanes. It can be obtained from macromolecules such as, but not limited to, polylactides, polycarbonates, polyamides and / or combinations thereof.

The elastic mesh material suitable for use within the mesh body 14 may take the form of a woven flat sheet, a woven sheet or a laser-cut wire mesh. In general, this material should contain two or more sets of substantially parallel strands, one set of parallel strands at 45-135 degrees to the other set of parallel strands. The pitch. In some embodiments, the two sets of parallel strands forming the mesh material are substantially perpendicular to each other. The pitch and overall structure of the mesh material may be optimized to meet the performance needs of the occlusion device.

The wire strands of the metal fabric used in the present invention should be made of a material that is elastic and can be heat treated to substantially set the desired shape. Materials considered to be suitable for this purpose include a cobalt-based low thermal expansion alloy called Elgiloy (registered trademark), and a nickel-based high-temperature commercially available product under the trade name Hastelloy (registered trademark) from Haynes International in the field of occlusion devices. High-strength "superalloys", nickel-based heat-treated alloys sold by International Nickel under the name Cobalt®, and many different grades of stainless steel. An important factor in choosing the right material for the wire is that the wire undergoes the proper amount of deformation (or shape memory as described below) caused by the molding surface when subjected to a given heat treatment. To hold.

One material class that satisfies these conditions is a so-called shape memory alloy. Such alloys tend to have a temperature-induced phase transition, which allows the material to have a preferred configuration that can be immobilized by heating the material above a certain transition temperature to induce a phase transition of the material. When the alloy is cooled, it "remembers" its shape during heat treatment and tends to adopt the same and / or similar configuration unless constrained to do so.

One particular shape memory alloy for use in the present invention is nitinol, a nearly stoichiometric alloy of nickel and titanium, which may also contain trace amounts of other metals to obtain the desired properties. NiTi alloys such as Nitinol, which include suitable compositions and handling requirements, are well known in the art and such alloys need not be elaborated here. For example, U.S. Pat. Nos. 5,067,489 and U.S. Pat. No. 4,991,602 (these teachings are incorporated herein by reference) are shape memory in guidewire-based technology. Discusses the use of NiTi alloys. Such NiTi alloys are preferred because, at least in part, they are commercially available and the handling of such alloys is better known than other well known shape memory alloys. NiTi alloys are also very elastic. In fact, NiTi alloys are said to be known as "superelastic" or "pseudoelastic". This elasticity helps the occlusion device disclosed herein revert to its previously extended configuration for its placement.

The wire strands may include standard monofilaments of the selected material. That is, standard wire stock may be used. In some embodiments, a configuration of 72 wire strands and / or 72 strand braids may be used. In other embodiments, the occlusion device comprises a wire mesh strand or braid that is a braided configuration of NiTi strands in the range 36-144. However, if desired, the individual wire strands may be formed from a "cable" composed of a plurality of individual wires. For example, a cable formed of a metal wire in which several wires are spirally wound around a center wire is commercially available, and a NiTi cable having an outer diameter of 0.003 inch or less is available for purchase. One advantage of some cables is that they tend to be "softer" than monofilament wires that have the same diameter and are made of the same material. In addition, the use of cables can increase the effective surface area of the wire strands and tends to promote thrombus formation.

The occlusion device disclosed herein is composed of a thin elastic mesh material with sufficient mesh density to function like a scaffold for endothelial cells within a blood vessel or across the neck 22 of an aneurysm 10. This reduces blood flow by about 60%, causing clot formation and / or healing of the aneurysm 10. For the purposes of the present invention, the term "mesh density" means the level of porosity or the ratio of metal to the opening area of the mesh body 14. The mesh density is related to the number and size of mesh openings or holes, and the degree to which the holes are open or closed in situations where the opening state of the openings or holes differs between delivery and indwelling. In general, the high mesh density region of the elastic mesh material has a metal area of approximately 40% or more and an opening area of about 60% or less.

In some embodiments, the elastic mesh body 14 may be uniformly formed of the same material. However, such materials may have different braided, sewn, braided and / or cut structures.

In other embodiments, the implantable occlusion device disclosed herein is a process of peripheral vascular embolization, a process well known in the art, of blood flow distal to a particular vascular site. It can be used to treat and / or ameliorate lesions of peripheral arteries or veins and / or any related lesions that require vascular occlusion to treat them) (known to be associated with arrest).

The occlusion device of the present invention may incorporate reasonable design parameters, features, modifications, advantages and variations that are obvious to those skilled in the art of occlusion devices.

The protocol and the legitimacy of animal use were reviewed and approved by the Instituteal Animal Care and Use Committee (IACUC) of ISIS Services, and the procedure was carried out under the supervision of a veterinarian.

The rabbit elastase aneurysm model is a widely accepted and art-approved model in the testing of novel neural interventional devices and has been published in many clinical publications regarding its efficacy and resemblance to human response. It has become an object of things. (For example, Altes et al. Creation of Aneurysms in the Rabbit: A Model Suitable for Testing Endovascular Devices. AJR 2000; 174: 349-354 as a model, and therefore an appropriate model. Approved immediately. The coagulation system of this model is very similar to the human coagulation system. In addition, this model has an advantageous anatomical aspect in that the diameter of the rabbit external carotid artery closely resembles the diameter of the human external carotid artery. Furthermore, elastase-induced aneurysms have been shown to behave histologically similar to human aneurysms.

Example I
Non-removable occlusion device lot 30680, detachable occlusion device lot 30676, aneurysm size 4.5 mm (mm) (height) x width 2.5.

A 5-F (5 French) sheath is placed in the femoral artery through which a 5F Cordis catheter, lumen 0.035 ", length 65 cm (cm), and 0.035" Terumo guide. Gained access to the carotid artery of the wire.

A non-withdrawal occlusion device was placed within the aneurysm with a marker on the neck of the aneurysm and contrast was flushed at regular intervals. Immediately after placement of the device, it was found to be in good position within the aneurysm, with some deceleration of blood flow. Five minutes after placement, some circulatory rest was observed within the aneurysm. Ten minutes after placement, further stagnation was noted within the aneurysm and the device was relocated closer to the aneurysm neck. Fifteen minutes after placement, stagnation of blood flow in the aneurysm was observed. When the device was removed from the aneurysm and heparin was administered, blood flow to the aneurysm returned to its pre-indwelling state.

The non-removable occlusion device was then removed and the 7 mm diameter occlusion device was advanced into a 0.027 "lumen microcatheter (Excelsior XT27, Stryker) using a 0.014" guide wire (Synchro2, Stryker). .. Note that the device advance within the catheter was smooth and low friction. The occlusive device was advanced to the neck of the aneurysm and placed in place. Regular angiography was performed. Immediately after placement, static blood flow was observed in the aneurysm. Five minutes after the indwelling, insufficient filling of the aneurysm was observed. A thrombus was found in the aneurysm 10 minutes after placement. Twenty minutes after the indwelling, the 5F catheter was taken out. Upon completion of the procedure, the animals were euthanized according to standard procedures (SOP).

Example II
Non-removable occlusion device lot 30680, withdrawal occlusion device lot 30676, aneurysm size height 10 mm x width 4 mm x neck 3 mm.

A non-withdrawal device was placed in the aneurysm neck and the same procedure as in Example I was performed. Note that in this example, a 4F system was used to introduce the device into the 5F sheath and hold the device by a "step" on the internal hub of the catheter. The device was placed and regular angiography was performed as before. Immediately after placement, some decrease in blood flow was observed in the aneurysm. Five minutes after the indwelling, insufficient filling in the aneurysm sac was observed. Ten minutes after indwelling, an increase in the size of underfilling was observed.

The device was removed and angiography revealed that blood flow in the aneurysm had returned to its pre-indwelling state, and an implantable (withdrawal) device was indwelled using the same method as before. The implant initially required some force to transition from the road sheath to the microcatheter (probably due to the unfamiliarity of the sheath and the hub lumen), but once inserted, the microcatheter advanced smoothly. ..

Note that the device has adequate indwelling control even though it is not anchored to the detachment mechanism. Positioning was performed so as to cover the neck of the aneurysm, and regular angiography was performed. Immediately after placement, a thrombus was found in the distal part of the aneurysm. Five minutes after placement, a de facto occlusion of the aneurysm sac was observed. Ten minutes after placement, complete occlusion of the aneurysm sac was observed. Fifteen minutes after placement, obstruction of the aneurysm was observed distal to the device marker.

Note that the active coagulation time (ACT) was twice the standard in the angiography 5 minutes after placement. Animal blood pressure was normal throughout the process (85/55, average 60-65 mm hg). This live animal will be reassessed 30 days after the study, as the placement of the device within the animal allowed blood circulation to rest without causing defects in the underlying carotid artery.

Example III
Detachable device lot 30676, aneurysm size 6.5 mm x width 3.1 mm x neck 2.4 mm.

This procedure followed the same implementation plan as in Example II. However, it was found that the aorta was dissociated when the contrast medium was injected. It was possible to place the device in the neck of the aneurysm. In addition, as before, regular angiography was performed.

Observations In this series of angiography, the wire mesh braid of the occlusion device disclosed herein is dense enough to reduce blood flow within the aneurysm, resulting in blood circulation retention and within the aneurysm sac. It was confirmed that it had led to a blood clot. This study, which takes into account the variability of animal morphology, has made it possible to develop devices and understand and consider their placement methods.

All femoral punctures were performed by femoral vein incision using a vein picker. The sheath used was 5-F, and in particular, it had a very narrow tip and allowed dilation of the femoral blood vessel without damaging the femoral blood vessel. Catheter length has become a problem, especially for devices that are fixed on wire. For this reason, shortened / hand-cut catheters were used in all cases. This means that the tip of the distal catheter is rather sharp and steep, leading to problems such as dissection of blood vessels as in Example III. Despite this (which can be addressed by the use of a microsheath), the placement of the occlusion device (with a large diameter guide catheter) was smooth and compatible with the use of the device with a detachment mechanism. ..

The operation and indwelling control of the occlusion device was performed while visualizing the radiopaque marker on the proximal side of the device to the tip of the catheter. The development of the device involves incorporating radiation-impermeable struts of platinum-core NiTi wire to aid visibility.

The occlusion device in animal studies was limited in expansion (7 mm). Device development incorporates an increased diameter of over 7 mm. Therefore, such devices have been designed with diameters of 11 mm and 14 mm. Even so, despite the limitation of dilation spread of the 7 mm device, all indwelling promotes perfusion within the aneurysm, and all devices guide, especially in the parent artery and the aneurysm's neck In addition, it was easy to operate with extremely accurate accuracy regarding the placement of the aneurysm in the aneurysm across the neck.

Some embodiments of the present invention have been described. Reasonable features, modifications, advantages and variations of the design of the claimed device, without departing from the scope and gist of the present invention, will be provided to those skilled in the art by the guidelines described in the detailed description and embodiments prior to them. Will be easily apparent by following. Therefore, other embodiments are within the scope of the following claims.

Claims (12)

Implantable devices for vascular occlusion, (a) a substantially solid marker having proximal and distal ends, and (b) an elastic mesh body attached to the distal end of the marker. The main body has a delivery shape and an indwelling shape that can be adapted to the blood vessel wall, and the main body is folded over itself to create a circumferential fold line around the main body. A double layer of elastic mesh folded back to the edges of the elastic mesh, all folded ends of the double layer of elastic mesh are within the marker.
Implantable device for vascular occlusion. The implantable device according to claim 1, wherein the indwelling shape of the main body can be juxtaposed with the aneurysm dome. The implantable device according to claim 1, wherein the main body can seal the neck of the aneurysm. The implantable device according to claim 1, wherein the marker is a radiation opaque marker. The implantable device according to claim 1, wherein the marker is a detachable connection portion for indwelling the implantable device. The implantable device according to claim 1, wherein the marker is a mounting connection portion for collecting the implantable device. The implantable device according to claim 4, wherein the marker includes a rigid member. The implantable device according to claim 1, wherein the marker is a solid ring. The first aspect of claim 1, wherein the body in free gas has a diameter larger than the diameter of the aneurysm or blood vessel to be treated, and the body has a height that is about 10-20% of its width. Implantable device. The implantable device of claim 9, wherein the body has a height of about 12-18% of its width. The implantable device of claim 9, wherein the body has a height of about 14-16% of its width. The implantable device of claim 9, wherein the body has a height of about 15% of its width.

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